Effect of mitochondrial division inhibitor on metabolic disorder of energy in hippocampus neurons of rats after cerebral ischemia-reperfusion injury

Objective To investigate the effect of mitochondrial division inhibitor (mdivi-1) on energy metabolism in hippocampus neurons of rats after ischemia reperfusion injury (IRI).Methods The hippocampus neurons fiom Wistar rats were in vitro cultured for 8 d and then,divided into four groups:normal control group,vehicle group,IRI+mdivi-1 treatment group and IRI group.IRI models in the later two groups were established by method of oxygen glucose deprivation; and pretreatment with mdivi-1 for 40 min was given to the IRI+mdivi-1 treatment group before IRI.After ischemia for 6 h and reperfusion for 20 h of hippocampus neurons,Western blotting was employed to examine the protein expressions of dynamin-related protein 1 (Drp1),B cell lymphoma/lewkmia-2 (Bcl-2) and Bcl-2 associated X protein (Bax); mitochondrial membrane potential (△Ψm) was examined by flow cytometry;enzyme standard instrument was used to examine the ATP content,mitochondrial complex activity,Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity.Results As compared with those in the normal control group,the expressions of Drp1 (1.001±0.276 and 1.985±0.301),Bax (2.752±0.786 and 4.225±1.107)were up-regulated markedly,those of Bcl-2 (0.749 ±0.128 and 0.336 ±0.109) were significantly down-regulated,percentage of low mitochondrial membrane potential △Ψm cells was significantly increased (72.5％ and 92.7％),ATP content ([74.129±5.773] and [36.986±5.945] μmol/gprot),Na+-K+-ATPaseactivity ([4.348±0.451] and [1.709±0.477] U/mgprot),Ca2+-Mg2+-ATPaseactivity([1.955±0.287] and [1.123 ±0.181] U/mgprot) and activities of mitochondrial complex Ⅰ,Ⅱ,Ⅲ and Ⅳ [(15.445±1.699),(17.065±1.070),(32.123±1.652),(2.814±0.180) and (6.810±1.725),(9.473±0.751),(23.010±1.716),(1.598±0.181)] nmol/(min ·mg) decreased in the IRI+mdivi-1 treatment group and IRI group,with significant differences (P＜ 0.05).IRI+mdivi-1 treatment group had markedly reduced Drp1 and Bax protein expressions,significantly improved Bcl-2 protein expression,significantly reduced percentage of low mitochondrial membrane potential △Ψm cells,and significantly increased brain ATP content,Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity,mitochondrial complex Ⅰ-Ⅳ activity as compared with IRI group (P＜0.05).Conclusion Mdivi-1,by inhibitting mitochondrial fission,can significantly improve mitochondrial energy metabolism and ameliorate cerebral ischemia/reperfusion injury. Key words: Mdivi-1;  Ischemia/reperfusion injury;  Energy metabolism;  Apoptosis